The convergence of fibrogenic and estrogen receptor signaling pathways: a target for multi-walled carbon nanotubes

Details

• Personal Author:
  Moreno S ; Porter DW ; Sabo-Attwood T ; Smith LC
• Description:
  Pulmonary fibrosis (PF) is an irreversible condition that if progressive can lead to potentially fatal lung disease characterized by organ malfunction and respiratory failure. PF can have unknown etiology as in idiopathic pulmonary fibrosis (IPF) or be associated with exposure to environmental agents such as asbestos fibers and potentially multi-walled carbon nanotubes (MWNT). The role of sex hormones and their receptors in PF is unclear despite the existence of sex-specific trends in the incidence and prevalence of IPF. The goal of this research is to examine a role for estrogen (E2) in fibrogenic signaling induced by MWNTs in bronchial epithelial cells (BEAS-2B). BEAS-2Bs were exposed to Mitsui MWNTs and estrogen receptor alpha (ESR1) gene expression was measured by qPCR. Results revealed a statistically significant (p < 0.05) 16, 48, and 56% reduction in ESR1 mRNA expression after 48 hr exposure to 0.2, 2, and 20 microg/mL MWNTs, respectively. Inhibition of transforming growth factor beta1 (TGF-beta1), a pro-fibrogenic cytokine shown to be up-regulated by MWNTs, using a receptor-specific inhibitor blocked the MWNT-induced reduction suggesting a role for TGF-beta1 in mediating the inhibitory effects. Next we performed an RNAseq analysis of BEAS-2Bs exposed to E2 in the presence and absence of TGF-beta1 to identify downstream targets of E2 that are susceptible to TGF-beta1 and potentially MWNTs. Results revealed distinct expression profiles where exposure to TGF-beta1 resulted in modulation of genes involved in extracellular matrix organization and cell adhesion by E2. Of the genes involved in cell adhesion, Muc15 emerged as a potential target of E2 as Muc15 exhibited a statistically significant (p < 0.05) Log2(Fold Change) of 2.09 in the E2 group, -4.61 in the TGF-beta1 group, and no statistically significant difference in the group co-exposed to TGF-beta1 and E2 suggesting that TGF-beta1 inhibited the E2-induced expression through inhibition of ESR1 gene expression. Current work is investigating Muc15 as a target for MWNTs. Results of this work highlight ESR1 and E2 target genes as potential targets of MWNTs in the lung. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Endocrine System Estrogens Fibrosis Genetics Growth Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

  More +
• Keywords:
  Carbon Nanotubes Cell Cultures Cell Culture Techniques Cell Signaling Cytokines Exposure Assessment Fibrogenicity Gene Expression Gene Regulation Genes Growth Factors Growth Inhibition Hormone Activity Hormones Lung Cells Lung Fibrosis Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Nanotubes Pulmonary Effects Pulmonary System Disorders Respiratory System Disorders Ribonucleic Acids RNA

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Florida ; Maryland ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049465
• Citation:
  Toxicologist 2017 Mar; 156(1):400
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:eb27c3d967d26cb79288c091d4fadf3c895de6c2d23f1efa32803802c75aa0903eda829be5d3d85c096373d367cd6003185da17654f7728db41a7bba9975c120
• Download URL:
  https://stacks.cdc.gov/view/cdc/203909/cdc_203909_DS1.pdf
• File Type:
  [PDF - 944.79 KB ]